Herpetic Stromal Keratitis (HSK) is an immunoinflammatory lesion of the cornea set off by herpes simplex virus (HSV) infection. This important cause of human blindness can be conveniently studied in mouse model systems where it has been shown that lesions are the consequence of a complex multistep process involving numerous molecular and cellular participants. The proposed research is designed to identify molecular signals that result from HSV infection of the corneal epithelium which cause rapid inflammatory changes in the underlying stroma. These include neutrophil infiltration and angiogenesis. The molecular signals are hypothesized to be multiple and include cytokines, chemokines, stress proteins, and fragments of viral DNA that are bioactive. The clinical and progressive phase of HSK depends on stimulation of CD4+ T cells which are hypothesized to enter the cornea once sufficient neovascularization has occurred. The research seeks to determine the mechanism by which CD4+ T cells are activated to contribute to tissue damage. Experiments are designed to define the respective roles of viral antigen specific and nonviral specific mechanisms of activation. Investigations also focus on angiogenesis during clinical HSK and the relevance of therapies designed to inhibit neovascularization.